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Magic Bullets

A Case on Enzyme Inhibition

By Sarah A. Wojiski

Magic Bullets


 

Abstract

This clicker case was designed to teach students about basic enzyme structure, mechanisms of enzyme inhibition, and mechanisms of drug resistance. The story follows Oliver Casey, a patient afflicted with Chronic Myelogenous Leukemia (CML). CML is caused by a chromosomal mutation that affects the tyrosine kinase ABL, an enzyme important in regulating cell growth and proliferation. The chromosomal mutation gives rise to the BCR-ABL fusion gene that produces a constitutively active ABL kinase, which causes the leukemia. In May 2001, the Food and Drug Administration approved the use of a rationally designed tyrosine kinase inhibitor, imatinib (Gleevec®), for the treatment of CML. During that same month, Gleevec made the cover of TIME magazine, described as "new ammunition in the war on cancer." The case is structured for a flipped classroom environment in which students view preparatory videos (including one by the author) on their own before beginning the case. Written for a first-year introductory biology course, the case could also be adapted for AP/Honors high school biology or a cancer biology course.

   

Date Posted

01/29/2016

Overview

Objectives

  • Define catalyst and describe the role of enzymes in biological systems.
  • Define substrate and active site, and explain the "induced fit" model of enzyme-substrate interactions.
  • Explain how different factors in the cellular environment, such as pH and temperature, affect enzyme activity.
  • Distinguish between competitive and non-competitive inhibition, and explain how competitive and non-competitive inhibitors alter an enzyme's activity.
  • Describe how enzyme inhibition can be used to treat certain forms of cancer.
  • Explain how mutations can lead to resistance to enzyme inhibition.

Keywords

Enzyme; enzyme inhibition; induced fit; kinase; leukemia; active site; substrate; competitive inhibition; chronic myelogenous leukemia; CML; hematopoiesis; Philadelphia chromosome; Gleevec; resistance

  

Subject Headings

Biology (General)
Cell Biology
Medicine (General)

EDUCATIONAL LEVEL

High school, Undergraduate lower division

  

FORMAT

PDF, PowerPoint

   

TOPICAL AREAS

N/A

   

LANGUAGE

English

   

TYPE/METHODS

Clicker, Flipped

 

 

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